Articular cartilage is an important component for the protection of bones in the body. In particular, articular cartilage functions to protect articulating bones from damage by providing a near-frictionless surface for bone movement and also providing compressive strength to joints. Articular cartilage broadly includes an extracellular matrix (ECM) derived from three main components: a collagen scaffold, hyaluronic acid (HA), and aggrecan. The material composition of articular cartilage dictates the tissue's biological, chemical and mechanical properties. The extracellular matrix (ECM) of healthy cartilage is primarily composed of a network of collagen fibrils (15-22% wet weight type II collagen), proteoglycans (4-7% wet weight), glycoproteins, water (60-85%) and electrolytes, giving rise to a viscoelastic tissue with depth-dependent structural and mechanical anisotropy.
Cartilage degradation and wear is a hallmark of osteoarthritis (OA). During the initial stages of OA, aggrecan, a major proteoglycan in cartilage, is an early component to be degraded. The aggrecan monomer is a protein core with covalently attached glycosaminoglycan (GAG) side chains that bind to filamentous hyaluronic acid via globular domains and a link protein. Proteases, such as aggrecanases, cleave aggrecan at specific sites creating protein fragments and free GAG chains that are unable to rebind to HA. Instead, these free GAG chains are extruded from the matrix, which not only reduces compressive strength, but also initiates an increase in pro-inflammatory cytokines and matrix metalloproteases. The presence of aggrecan has been shown to reduce diffusion of proteases protecting underlying collagen fibers from proteolytic cleavage. Loss of aggrecan occurs even in normal cartilage and is not immediately correlated to OA. However, loss of type II collagen is considered an irreversible process, leading to precocious wear.
Osteoarthritis is the most common form of arthritis, affecting 27 million people in the US alone. The most prevalent symptoms of osteoarthritis include immense pain, stiffening in the joints, and tender and inflamed joints. Advanced stages of osteoarthritis can lead to complete degradation of the articular cartilage, causing immobility of joints and damage to the underlying bone. The direct costs of arthritis in the United States are estimated to be approximately $185.5 billion each year.
Although lifestyle changes and multiple medications are often used for the treatment of osteoarthritis, there has been little success in regeneration of defective cartilage and relieving the symptoms caused by the loss of cartilage. This inability to halt the progression of osteoarthritis and repair the existing damage typically leads to an invasive, end stage cartilage replacement procedure. Thus, an alternative treatment option for osteoarthritis is highly desired.
The present disclosure describes improved biomaterials for cartilage regeneration, including hyaluronic acid-binding synthetic peptidoglycans that can be utilized to restore damaged cartilage in an affected patient, along with methods of forming and using the synthetic peptidoglycans. Furthermore, the hyaluronic acid-binding synthetic peptidoglycans are designed to functionally mimic aggrecan, resist aggrecanase degradation, and limit proteolytic degradation. The absence of the native amino acid sequence seen in aggrecan makes these molecules less susceptible to proteolytic cleavage.
The following numbered embodiments are contemplated and are non-limiting:                1. A hyaluronic acid-binding synthetic peptidoglycan comprising a synthetic peptide conjugated to a glycan wherein the synthetic peptide comprises a hyaluronic acid-binding sequence.        2. The synthetic peptidoglycan of clause 1 wherein the synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        3. The synthetic peptidoglycan of clause 1 or clause 2 wherein the synthetic peptide comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                4. The synthetic peptidoglycan of any one of clauses 1 to 3 wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        5. The synthetic peptidoglycan of any one of clauses 1 to 4 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        6. The synthetic peptidoglycan of any one of clauses 1 to 5 wherein the synthetic peptidoglycan is resistant to aggrecanase.        7. The synthetic peptidoglycan of any one of clauses 1 to 6 wherein the synthetic peptidoglycan is lyophilized.        8. A compound of formula PnGx wherein n is 1 to 20;                    wherein x is 1 to 20;            wherein P is a synthetic peptide of about 5 to about 40 amino acids comprising a hyaluronic acid binding sequence; and            wherein G is a glycan.                        9. A compound of formula (PnL)xG wherein n is 1 to 20;                    wherein x is 1 to 20;            wherein P is a synthetic peptide of about 5 to about 40 amino acids comprising a hyaluronic acid binding sequence;            wherein L is a linker; and wherein G is a glycan.                        10. A compound of formula P(LGn)x wherein n is 1 to 20;                    wherein x is 1 to 20;            wherein P is a synthetic peptide of about 5 to about 40 amino acids comprising a hyaluronic acid binding sequence;            wherein L is a linker; and            wherein G is a glycan.                        11. A compound of formula PnGx wherein n is MWG/1000;                    wherein MWG is the molecular weight of G rounded to the nearest 1 kDa;            wherein x is 1 to 20;            wherein P is a synthetic peptide of about 5 to about 40 amino acids comprising a hyaluronic acid binding sequence; and            wherein G is a glycan.                        12. A compound of formula (PnL)xG wherein n is MWG/1000;                    wherein MWG is the molecular weight of G rounded to the nearest 1 kDa;            wherein x is 1 to 20;            wherein P is a synthetic peptide of about 5 to about 40 amino acids comprising a hyaluronic acid binding sequence;            wherein L is a linker; and wherein G is a glycan.                        13. The compound of any one of clauses 8 to 12 wherein the synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        14. The compound of any one of clauses 8 to 13 wherein the synthetic peptide comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                15. The compound of any one of clauses 8 to 14 wherein the glycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        16. The compound of any one of clauses 8 to 15 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        17. The compound of any one of clauses 8 to 16 wherein the synthetic peptidoglycan is resistant to aggrecanase.        18. An engineered collagen matrix comprising polymerized collagen, hyaluronic acid, and a hyaluronic acid-binding synthetic peptidoglycan.        19. The engineered collagen matrix of clause 18 wherein the collagen is selected from the group consisting of type I collagen, type II collagen, type III collagen, type IV collagen, type IX collagen, type XI collagen, and combinations thereof        20. The engineered collagen matrix of clause 18 or 19 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        21. The engineered collagen matrix of any one of clauses 18 or 20 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                22. The engineered collagen matrix of any one of clauses 18 to 21 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        23. The engineered collagen matrix of any one of clauses 18 to 22 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        24. The engineered collagen matrix of any one of clauses 18 to 23 wherein the synthetic peptidoglycan is resistant to aggrecanase.        25. The engineered collagen matrix of any one of clauses 18 to 24 wherein the matrix is effective as a tissue graft.        26. The engineered collagen matrix of clause 25 wherein the tissue graft is implanted into a patient.        27. The engineered collagen matrix of any one of clauses 18 to 24 wherein the matrix is in the form of a gel.        28. The engineered collagen matrix of clause 27 wherein the gel is administered to a patient by injection.        29. The engineered collagen matrix of any one of clauses 18 to 24 wherein the matrix is effective as a composition for in vitro culture of cells.        30. The engineered collagen matrix of clause 29 wherein the matrix further comprises an exogenous population of cells.        31. The engineered collagen matrix of clause 30 wherein the cells are selected from the group consisting of chondrocytes and stem cells.        32. The engineered collagen matrix of clause 31 wherein the stem cells are selected from the group consisting of osteoblasts, osteogenic cells, and mesenchymal stem cells.        33. The engineered collagen matrix of any one of clauses 18 to 32 further comprising one or more nutrients.        34. The engineered collagen matrix of any one of clauses 18 to 33 further comprising one or more growth factors.        35. The engineered collagen matrix of any one of clauses 18 to 34 wherein the matrix is sterilized.        36. A composition for in vitro culture of chondrocytes or stem cells comprising a hyaluronic acid-binding synthetic peptidoglycan.        37. The composition of clause 36 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        38. The composition of clause 36 or clause 37 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                39. The composition of any one of clauses 36 to 38 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        40. The composition of any one of clauses 36 to 39 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        41. The composition of any one of clauses 36 to 40 wherein the synthetic peptidoglycan is resistant to aggrecanase.        42. The composition of any one of clauses 36 to 41 wherein the stem cells are selected from the group consisting of osteoblasts, osteogenic cells, and mesenchymal stem cells.        43. The composition of any one of clauses 36 to 42 further comprising one or more nutrients.        44. The composition of any one of clauses 36 to 43 further comprising one or more growth factors.        45. The composition of any one of clauses 36 to 44 wherein the composition is sterilized.        46. An additive for a biomaterial cartilage or bone replacement composition comprising a hyaluronic acid-binding synthetic peptidoglycan for addition to an existing biomaterial cartilage or bone replacement material.        47. The additive of clause 46 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        48. The additive of clause 46 or clause 47 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK; (SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                49. The additive of any one of clauses 46 to 48 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        50. The additive of any one of clauses 46 to 49 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        51. The additive of any one of clauses 46 to 50 wherein the synthetic peptidoglycan is resistant to aggrecanase.        52. A method of treatment for arthritis in a patient, said method comprising the step of administering to the patient a hyaluronic acid-binding synthetic peptidoglycan, wherein the synthetic peptidoglycan reduces a symptom associated with the arthritis.        53. The method of clause 52 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        54. The method of clause 52 or clause 53 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                55. The method of any one of clauses 52 to 54 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        56. The method of any one of clauses 52 to 55 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        57. The method of any one of clauses 52 to 56 wherein the synthetic peptidoglycan is resistant to aggrecanase.        58. The method of any one of clauses 52 to 57 wherein the arthritis is osteoarthritis.        59. The method of any one of clauses 52 to 57 wherein the arthritis is rheumatoid arthritis.        60. The method of any one of clauses 52 to 59 wherein the synthetic peptidoglycan is administered to the patient by injection.        61. The method of clause 60 wherein the injection is an intraarticular injection.        62. The method of clause 60 wherein the injection is into a joint capsule of the patient.        63. The method of any one of clauses 52 to 62 wherein the synthetic peptidoglycan is administered using a needle or a device for infusion.        64. The method of any one of clauses 52 to 63 wherein the synthetic peptidoglycan acts as a lubricant.        65. The method of any one of clauses 52 to 64 wherein the synthetic peptidoglycan prevents bone on bone articulation or prevents cartilage loss.        66. A method of preparing a biomaterial or bone cartilage replacement, said method comprising the step of combining the synthetic peptidoglycan and an existing biomaterial or bone cartilage replacement material.        67. The method of clause 66 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        68. The method of clause 66 or clause 67 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                69. The method of any one of clauses 66 to 68 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        70. The method of any one of clauses 66 to 69 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        71. The method of any one of clauses 66 to 70 wherein the synthetic peptidoglycan is resistant to aggrecanase.        72. A method of reducing or preventing hyaluronic acid degradation in a patient, said method comprising administering to the patient a hyaluronic acid-binding synthetic peptidoglycan.        73. The method of clause 72 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        74. The method of clause 72 or clause 73 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus                75. The method of any one of clauses 72 to 74 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        76. The method of any one of clauses 72 to 75 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        77. The method of any one of clauses 72 to 76 wherein the synthetic peptidoglycan is resistant to aggrecanase.        78. The method of any one of clauses 72 to 77 wherein the synthetic peptidoglycan is administered to the patient by injection.        79. The method of clause 78 wherein the injection is an intraarticular injection.        80. The method of clause 78 wherein the injection is into a joint capsule of the patient.        81. The method of any one of clauses 72 to 80 wherein the rate of hyaluronic acid degradation is reduced.        82. A method for correcting or modifying a tissue defect in a patient comprising                    administering into the tissue defect a hyaluronic acid-binding synthetic peptidoglycan wherein the defect is corrected or modified.                        83. The method of clause 82 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        84. The method of clause 82 or clause 83 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                85. The method of any one of clauses 82 to 84 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        86. The method of any one of clauses 82 to 85 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        87. The method of any one of clauses 82 to 86 wherein the synthetic peptidoglycan is resistant to aggrecanase.        88. The method of any one of clauses 82 to 87 wherein the synthetic peptidoglycan is administered to the patient by injection.        89. The method of clause 88 wherein the injection is subcutaneous.        90. The method of any one of clauses 82 to 89 wherein the defect is a cosmetic defect.        91. A dermal filler comprising a hyaluronic acid-binding synthetic peptidoglycan.        92. The dermal filler of clause 91 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2, wherein X8 is present or is not present, wherein B1 is a basic amino acid, wherein B2 is a basic amino acid, and wherein X1-X8 are non-acidic amino acids.        93. The dermal filler of clause 91 or clause 92 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)
In each of the above peptide embodiments, the peptide may have a glycine-cysteine (GC) attached to the C-terminus of the peptide, or a glycine-cysteine-glycine (GCG) attached to the N-terminus.                94. The dermal filler of any one of clauses 91 to 93 further comprising hyaluronic acid.        95. A method of reducing or preventing collagen degradation, said method comprising the steps of                    contacting a hyaluronic acid-binding synthetic peptidoglycan with hyaluronic acid in the presence of collagen, and            reducing or preventing collagen degradation.                        96. The method of clause 95 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        97. The method of clause 95 or clause 96 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)                98. The method of any one of clauses 95 to 97 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        99. The method of any one of clauses 95 to 98 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        100. The method of any one of clauses 95 to 99 wherein the synthetic peptidoglycan is resistant to aggrecanase.        101. The method of any one of clauses 95 to 100 wherein the rate of hyaluronic acid degradation is reduced.        102. A method of increasing pore size in an engineered collagen matrix, said method comprising the steps of                    combining collagen, hyaluronic acid, and a hyaluronic acid-binding synthetic peptidoglycan, and            increasing the pore size in the matrix.                        103. The method of clause 102 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        104. The method of clause 102 or clause 103 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)                105. The method of any one of clauses 102 to 104 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        106. The method of any one of clauses 102 to 105 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        107. The method of any one of clauses 102 to 106 wherein the synthetic peptidoglycan is resistant to aggrecanase.        108. The method of any one of clauses 102 to 107 wherein the matrix is sterilized.        109. The method of any one of clauses 102 to 108 wherein the matrix further comprises chondrocytes or stem cells.        110. The method of clause 109 wherein the stem cells are selected from the group consisting of osteoblasts, osteogenic cells, and mesenchymal stem cells.        111. The method of any one of clauses 102 to 110 wherein the matrix further comprises one or more nutrients.        112. The method of any one of clauses 102 to 111 wherein the matrix further comprises one or more growth factors.        113. A method of reducing or preventing chondroitin sulfate degradation, said method comprising the steps of                    contacting a hyaluronic acid-binding synthetic peptidoglycan with hyaluronic acid in the presence of collagen, and            reducing or preventing chondroitin sulfate degradation.                        114. The method of clause 113 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 (SEQ ID NO: 1),                    wherein X8 is present or is not present,            wherein B1 is a basic amino acid,            wherein B2 is a basic amino acid, and            wherein X1-X8 are non-acidic amino acids.                        115. The method of clause 113 or clause 114 wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence selected from the group consisting of:        
GAHWQFNALTVRGG;(SEQ ID NO: 2) GDRRRRRMWHRQ;(SEQ ID NO: 3) GKHLGGKHRRSR;(SEQ ID NO: 4) RGTHHAQKRRS;(SEQ ID NO: 5) RRHKSGHIQGSK;(SEQ ID NO: 6) SRMHGRVRGRHE;(SEQ ID NO: 7) RRRAGLTAGRPR;(SEQ ID NO: 8) RYGGHRTSRKWV;(SEQ ID NO: 9) RSARYGHRRGVG;(SEQ ID NO: 10) GLRGNRRVFARP;(SEQ ID NO: 11) SRGQRGRLGKTR;(SEQ ID NO: 12) DRRGRSSLPKLAGPVEFPDRKIKGRR;(SEQ ID NO: 13) RMRRKGRVKHWG;(SEQ ID NO: 14) RGGARGRHKTGR;(SEQ ID NO: 15) TGARQRGLQGGWGPRHLRGKDQPPGR;(SEQ ID NO: 16) RQRRRDLTRVEG;(SEQ ID NO: 17) STKDHNRGRRNVGPVSRSTLRDPIRR;(SEQ ID NO: 18) RRIGHQVGGRRN;(SEQ ID NO: 19) RLESRAAGQRRA;(SEQ ID NO: 20) GGPRRHLGRRGH;(SEQ ID NO: 21) VSKRGHRRTAHE;(SEQ ID NO: 22) RGTRSGSTR;(SEQ ID NO: 23) RRRKKIQGRSKR;(SEQ ID NO: 24) RKSYGKYQGR;(SEQ ID NO: 25) KNGRYSISR;(SEQ ID NO: 26) RRRCGQKKK;(SEQ ID NO: 27) KQKIKHVVKLK;(SEQ ID NO: 28) KLKSQLVKRK;(SEQ ID NO: 29) RYPISRPRKR;(SEQ ID NO: 30) KVGKSPPVR;(SEQ ID NO: 31) KTFGKMKPR;(SEQ ID NO: 32) RIKWSRVSK;(SEQ ID NO: 33)and KRTMRPTRR.(SEQ ID NO: 34)                116. The method of any one of clauses 113 to 115 wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparan, heparin, keratin, keratan sulfate, and hyaluronic acid.        117. The method of any one of clauses 113 to 116 wherein the glycan is selected from the group consisting of chondroitin sulfate and keratan sulfate.        118. The method of any one of clauses 113 to 117 wherein the synthetic peptidoglycan is resistant to aggrecanase.        119. The method of any one of clauses 113 to 118 wherein the rate of chondroitin sulfate degradation is reduced.        120. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of any of the preceding clauses wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine (GC) attached to the C-terminus of the peptide.        121. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of any of the preceding clauses wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine-glycine (GCG) attached to the N-terminus of the peptide.        122. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of any of the preceding clauses wherein the synthetic peptidoglycan is resistant to matrix metallo proteases.        123. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of clause 122 wherein the matrix metallo protease is aggrecanase.        124. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of any of the preceding clauses wherein the dosage of the synthetic peptidoglycan is in a concentration ranging from about 0.01 uM to about 100 uM.        125. The synthetic peptidoglycan, compound, engineered collagen matrix, composition, additive, method, or dermal filler of any of the preceding clauses wherein the dosage of the synthetic peptidoglycan is in a concentration ranging from about 0.1 uM to about 10 uM.        